What is your lab’s long-term/big-picture research goal?
Our laboratory is primarily focused on cancer research. We are currently examining two enzymes—JMJD and DNPH1—that are relevant to the formation of tumors and their response to therapy. The JMJD proteins can modify histone proteins, which tightly associate with DNA and determine how efficiently a gene is expressed. In tumors, several of the JMJD proteins are either up- or down-regulated, which leads to profound changes in the expression of cancer-critical genes. Our long-term objective is to understand how dysregulation of JMJD proteins stimulates cancer cells. We want to provide knowledge about how to prevent cancer cell metastasis, including through the development of small molecules that regulate JMJD activity. Currently, we focus on the role of JMJD proteins in breast, pancreatic, and testicular germ cell tumors, and we hope to improve survival of patients with these malignancies. Likewise, we are interested in finding inhibitors for DNPH1, an enzyme that can make cancer cells resistant to a class of drugs clinically approved for treating breast, ovarian, and pancreatic cancers. Acquired or initial resistance to therapy occurs in about half of all cancer patients, often leading to their demise. This is why it is so important to identify ways of re-sensitizing cancer cells to chemotherapeutic drugs through new approaches like inhibiting DNPH1. In general, our predominant research efforts are directed at understanding the molecular defects of cancer cells, which we believe will lead to insights that will improve patients’ quality and length of life.
What is your training/scientific background?
I received my undergraduate and graduate training at the University of Bochum, Germany, with a focus on biochemistry. Thereafter, I obtained postdoctoral training at Hannover Medical School, Germany, and the Salk Institute, La Jolla, California, where I studied fundamental processes in gene expression. In 1998, I started my independent research laboratory at the Mayo Clinic in Rochester, Minnesota, before transitioning to the University of Oklahoma Health Sciences Center in 2009, where I am currently a Professor of Cell Biology and a member of the Stephenson Cancer Center. Within my laboratory, we have analyzed how various proteins affect gene transcription, epigenetics, and intracellular signaling. Although cancer is the main focus of my laboratory, we have also studied developmental processes.
What is the goal of your OCASCR project?
We serendipitously found that one of the JMJD proteins (JMJD5) is absolutely required for male fertility. More detailed analysis implied that JMJD5 affects male germ stem cells. The first goal of our project is to uncover how JMJD5 ablation leads to male infertility. This may suggest ways to help the ~10% of males who are infertile in the US and conversely may lead to the development of male contraceptives. The second part of our project deals with abnormal male germ stem cells that can be found in testicular germ cell tumors. We will decipher how JMJD5 promotes this tumor type, which could suggest potential avenues of future therapy, including through the inhibition of JMJD5 by small molecule drugs.
How might your research impact diseases related to obesity or smoking?
Obesity and smoking are probably the most significant risk factors for cancer development in the US. Epigenetic changes are observable in obese persons and smokers, strongly suggesting that they are also underlying causes for the promotion of cancer development. JMJD proteins are epigenetic regulators, and hence our studies could shed light on their potential role in obesity and smoking-related tumors (e.g., liver, endometrial, or lung cancers). Such knowledge can be leveraged in the design of new therapies.
What is your favorite scientific meeting to attend? Why?
I prefer to attend smaller meetings that allow for intense interactions with other scientists and have a focused agenda. Also, I like meetings related to novel research directions in my laboratory, since they provide a fast introduction into and a quite comprehensive overview about research areas that are new to me.